It is often difficult to distinguish histologically between an adrenal cortical cancer and a benign adenoma, or to predict the prognosis of patients with adrenal cortical cancers. In this investigation, we examined whether apoptosis-regulating genes, bcl-xL and fas, and a telomere-related gene, telomeric-repeat binding factor-1 (TRF-1), differ between adrenal cortical cancers and benign adrenal tumors. Tissues from 4 adrenal cortical cancers were compared with 7 normal adrenal tissues, 17 cortical adenomas, 4 cortical hyperplasias, and 20 pheochromocytomas for expressions of bcl-xL and fas by RT-PCR, and for expressions of TRF-1 by real-time quantitative RT-PCR. All benign adrenal tissues expressed both the antiapoptosis gene, bcl-xL, and proapoptosis gene, fas, but the adrenal cortical cancers expressed only bcl-xL and not fas. TRF-1 increased by more than 30-fold in the adrenal cortical cancers, compared with benign adrenal tissues, and inversely correlated with the prognosis of patients with the adrenal cortical cancers. This lack of expression of fas in adrenal cortical cancer may help to distinguish it from benign adrenal tumors. The level of TRF-1 expression may be helpful prognostically for patients with adrenal cortical cancers.